The transferrins, a class of iron-binding proteins widely distributed in physiological fluids and cells, fulfill essential roles in the transport and metabolism of iron. Our goal is to understand the structural foundations and molecular mechanisms underlying their biological functions. In pursuing this, we have chosen to study: (1) the remarkable cooperativity between the metal and anion binding sites of the transferrins, utilizing electron and nuclear magnetic resonance spectroscopy; (2) the molecular events during the interaction of serum transferrin with the reticulocyte, when the protein serves to provide iron for the biosynthesis of hemoglobin, with particular emphasis on the reticulocyte receptor for transferrin; (3) the mechanisms governing the transfer of iron between transferrin and ferritin to try to clarify the biochemical interrelationships of these iron-binding proteins. Such research should lead not only to elucidation of the normal events in iron metabolism, but ultimately to more rational and effective therapy of derangements in the utilization of this essential metal - among the most common and widespread of man's disorders.